Dr. Weeks’ Comment: Inflammation drives cancer. Take your safe and effective anti-inflammatory seeds!
Pancreas. 2017 Sep;46(8):973-985. doi: 10.1097/MPA.0000000000000886.
Inflammation-Related Pancreatic Carcinogenesis: Mechanisms and Clinical Potentials in Advances.
Dai JJ1, Jiang MJ, Wang XP, Tian L.
Chronic inflammation has long been considered critical in pancreatic carcinogenesis, and recently studies showed that some anti-inflammatory agents such as aspirin could potentially be used to attenuate pancreatic carcinogenesis. Several inflammation-related critical transcription factors and pathways such as NF-κB (nuclear factor κ-light-chain enhancer of activated B cells) and reactive oxygen species have been confirmed to be involved in carcinogenesis. However, its underlying mechanisms are far from clear, which largely limits further development of potential anticarcinogenesis drugs. As a result, it is of great importance for us to better understand and gain a better perspective in inflammation-related pancreatic carcinogenesis. In this review, we systematically analyzed recent advances concerning inflammation-related pancreatic carcinogenesis and brought out the possible underlying mechanisms. Potential preventive and therapeutic strategies based on anti-inflammatory agents have also been further discussed.
Int J Oncol. 2006 Jul;29(1):185-92.
NF-kappaB, inflammation and pancreatic carcinogenesis: NF-kappaB as a chemoprevention target (review).
Pancreatic cancer is the most deadly of all gastrointestinal malignancies with near zero five-year survival. This review summarizes our understanding of the potentially important role of inflammation in cancer in general and pancreatic cancer in particular. Nuclear factor kappaB (NF-kappaB), a mediator of inflammatory responses, plays a significant role in carcinogenesis and is now emerging as a link between inflammation and cancer. NF-kappaB is activated in over two thirds of human pancreatic cancers; participates in early events of pancreatic carcinogenesis through its interactions with signaling pathways; and suppression of its activation restores pancreatic cell kinetics, mainly normalizing the suppressed apoptosis of pancreatic cancer. NF-kappaB is an excellent target for chemoprevention and its modulation for pancreatic cancer prevention appears promising. The next few years will likely expand our understanding of NF-kappaB biology; solidify NF-kappaB’s role as a major link between chronic inflammation and pancreatic carcinogenesis; and witness the development of NF-kappaB-based approaches to pancreatic cancer prevention.
Curr Cancer Drug Targets. 2005 Aug;5(5):325-44.
Inflammation and cancer: when NF-kappaB amalgamates the perilous partnership.
Chronic inflammation has long been suggested to constitute a risk factor for a variety of epithelial cancers such as malignancies of prostate, cervix, esophagus, stomach, liver, colon, pancreas, and bladder. An inflammatory response is typically accompanied by generation of free radicals, stimulation of cytokines, chemokines, growth and angiogenic factors. Free radicals, capable of both directly damaging DNA and affecting the DNA repair machinery, enhance genetic instability of affected cells, thus contributing to the first stage of neoplastic transformation also known as “initiation”. Cytokines and growth factors can further promote tumor growth by stimulating cell proliferation, adhesion, vascularization, and metastatic potential of later stage tumors. Nuclear factor kappa B (NF-kappaB) is a family of ubiquitously expressed transcription factors that are widely believed to trigger both the onset and the resolution of inflammation. NF-kappaB also governs the expression of genes encoding proteins essential in control of stress response, maintenance of intercellular communications, and regulation of cellular proliferation and apoptosis. Recent data have expanded the concept of inflammation as a critical component in carcinogenesis suggesting new anti-inflammatory therapies for a complementary approach in treating a variety of tumor types. These observations highlighted the NF-kappaB pathway as an attractive avenue for drug discovery and development. The present review will outline recent advances in our understanding of NF-kappaB function in the inflammatory processes and its input in tumor initiation/promotion, as well as summarize the development of animal and cell culture models for validating drug candidates with NF-kappaB-modulating activities, and applications of the latter in cancer therapy.
PLoS One. 2016 Feb 12;11(2):e0149028. doi: 10.1371/journal.pone.0149028. eCollection 2016.
Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis.
Fan X1, Zhang X1, Shen J1, Zhao H2, Yu X1, Chen Y1, Zhuang Z3, Deng X1, Feng H1, Wang Y1, Peng L1.
- Correction: Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis. [PLoS One. 2016]
Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 expression was found to be suppressed both at mRNA and protein levels in cell line models as well as in clinical samples; decreased TUSC3 expression was associated with higher pathological TNM staging and poorer outcome. In three pairs of cell lines with different NF-κB activity, TUSC3 expression was found to be reversely correlated with NF-κB activity. TUSC3-silenced pancreatic cancer cell line exhibited enhanced potential of proliferation, migration and invasion. In an orthotopic implanted mice model, TUSC3 silenced cells exhibited more aggressive phenotype with more liver metastasis. In conclusion, the current study shows that decreased immunological TUSC3 staining is a factor prognostic of poor survival in pancreatic cancerpatients and decreased TUSC3 promotes pancreatic cancer cell proliferation, invasion and metastasis. The reverse correlation between NF-κB activity and TUSC3 expression may suggest a novel regulation pattern for this molecule.